E2F1 Orchestrates Transcriptomics and Oxidative Metabolism in Wharton's Jelly-Derived Mesenchymal Stem Cells from...

Area of Science:

• Cell Biology
• Metabolic Research
• Stem Cell Biology

Background:

• Wharton's jelly-derived Mesenchymal Stem Cells (MSCs) from intrauterine growth restriction newborns exhibit anabolic properties.
• Previous studies indicated insulin hypersensitivity in these MSCs.

Purpose of the Study:

• To investigate mitochondrial function in MSCs from small for gestational age (SGA) individuals.
• To identify molecular mechanisms underlying metabolic alterations in SGA MSCs.
• To explore the role of E2F1 and its downstream targets in SGA MSCs.

Main Methods:

• Isolation and characterization of MSCs from normally grown and SGA newborns.
• Mitochondrial oxygen consumption rate measurements.
• Next-generation sequencing for transcriptomic and epigenetic profiling.
• Analysis of transcription factor E2F1 and histone modifications (H3K27ac, H3K4me3).
• Investigation of the fatty acid elongase ELOVL2 and docosahexaenoic acid (DHA) synthesis.

Main Results:

• MSCs from SGA individuals displayed decreased mitochondrial oxygen consumption rates.
• E2F1 was identified as an over-expressed transcription factor in SGA MSCs, regulating oxidative metabolism.
• E2F1 was associated with activating histone marks (H3K27ac, H3K4me3) and differential gene expression.
• The E2F1-regulated gene ELOVL2, involved in DHA synthesis, was identified as a key player.

Conclusions:

• The E2F1-ELOVL2 pathway significantly influences oxidative metabolism in SGA MSCs.
• This pathway contributes to maintaining cellular metabolic homeostasis in the context of SGA.
• Findings provide insights into the molecular basis of metabolic dysfunction in SGA-derived MSCs.